Sodium Chlorite Listed as Active Ingredient in Anti-Fungal/Anti-Bacterial Fish Medication

Question

My hobby is Fish Keeping. About 6 months ago I picked up a medication called Maracyn Oxy. It's a non-antibiotic treatment for true fungal and some bacterial infections and it works like an absolute charm!

However, nobody in the hobby seems to know exactly how it works. The active ingredient is sodium chlorite.

Back of the bottle:

INSTRUCTIONS: 1/2 capful (1/2 tsp/2.4mL) per 10 gallons (38 liters) of water. Repeat daily as needed for more than five days. It is suggested to always increase tank aeration during treatment to ensure there is an adequate oxygen supply for infected fish. Turn off UV Sterilizers during treatment. Should fish exhibit signs of distress, neutralize the medication by using an aquarium dechlorinator (like FritzGuard), follow manufacturers directions for dosing. Use of a hospital tank is recommended. No water changes, pH or temperature adjustments necessary if readings are in ideal range. Maintain normal filtration.

So I went down a rabbit hole. Below I've outlined my theory.

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Chlorine Dioxide?

I don't think that sodium chlorite itself is what is actually what is killing the harmful microorganisms. Most of the articles I've found talk about it being used to create Chlorine Dioxide - especially in water treatment plants where it is used to kill bacteria and etc.

After a couple more Google searches I found this article that cites the following:

First, (equation 1), chlorine reacts with water to form hypochlorous acid (HOCl) and hydrochloric acid (HCl). These acids react (equation 2) with sodium chlorite to form chlorine dioxide, water, and sodium chloride (NaCl).

The reason I included the instructions on the back of the bottle is because of two statements that I believe help this theory:

1. "Turn off UV Sterilizers during treatment" - I've read several articles that state that UV light is effective in neutralizing CLO2.
2. "Should fish exhibit signs of distress, neutralize the medication by using an aquarium dechlorinator" - according to this article (from the same organization as the other) although sodium sulfite is most effective, sodium thiosulfate (a common ingredient in tap water conditioners) can neutralize concentrated solutions of sodium chlorite.

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I'd love to learn:

1. Am I probably right about Chlorine Dioxide? If not, what is more likely?
2. If so would it be that it's chlorine + sodium chlorite that's actually in the bottle, and the chlorine dioxide gets created when added to the water?

If my tags are off I appreciate any help.

Answer 1

The chemistry of chlorine is complex, with many possible species of different oxidation states. The company selling the product has a safety data sheet (SDS) that states the ingredients as propriatary, but then classifies the product as chlorite solution for transport. Chlorite $\ce{ClO2-}$ (and chlorous acid, $\ce{HClO2}$) have a +3 oxidation state, chlorine dioxide a +4 oxidation state, hypochlorite (active ingredient in bleach, $\ce{ClO-}$) a +1 oxidation state, and the chloride ion (in table salt) a -1 oxidation state.

Source: https://www.onlinechemistrytutor.net/oxidation-state-examples/

What it probably is not

Chlorite, as stated by the OP, can be used to synthesize chlorine dioxide gas by adding chlorine or hypochlorite. It is unlikely that there is chlorine or hypochlorite in the product.

Chlorite in an acidified form is used as desinfection agent to kill bacteria on chicken and cows during meat processing. In this application, chlorine dioxide is produced:

$$\ce{4 HClO2 -> 2 ClO2 + ClO3- + Cl- + 2H+ + H2O}$$ $$\ce{5 HClO2 -> 4ClO2 + Cl- + H+ + 2 H2O}$$

A strongly acidic solution (very low pH) would probably kill the fish, so that formulation is also unlikely.

What it might be

There is a product for cleaning contact lenses where chlorite is combined with sodium chloride and trace amounts of hydrogen peroxide.

Source: https://www.sciencedirect.com/topics/medicine-and-dentistry/sodium-chlorite

This is a possible formulation. A putative mechanism of action is discussed here: http://advancedeyecareresearch.co.uk/pdf/regard.pdf, but they don't say much about the chemistry. The key is to have a formulation that is stable until it comes in contact with the organisms you want to kill, and does not kill the fish, plants and snails.

Mechanism of action

Chlorite is toxic for vertebrates, bacteria, fungi, and other organisms. The claims that it has benefits as part of a "Miracle Mineral Solution" are false and dangerous; ingesting chlorite is life-threatening, damaging kidneys, intestines and the hemoglobin in our red blood cells.

Some micro-organisms have a dedicated chlorite dismutase enzyme that breaks down chlorite into chloride and dioxygen. Organisms that break down perchlorates have these enzymes; more recently, they were also find in ammonium-utilizing bacteria.

In the absence of chlorite dismutase (or when administering doses that are to high for efficient detoxification), the chlorite ions could have multiple damaging and deadly effects. In humans, the iron in hemoglobin is oxidized from the +2 to the +3 oxidation state (the hemoglobin is called methemoglobin), interfering with oxygen transport.

In a study on the toxic effect of chlorite on mammalian cells and on microorganisms, glutothione (an intracellular redox buffer) was readily oxidized by chlorite. The authors saw this as evidence that chlorite imposes oxidative stress on cells.

It would be very difficult to state the exact chemical reactions going on in the cell when exposed to chlorite. The chlorine chemistry is rich, and there are thousands of possible reaction partners in the cell. Fish "medication" is not controlled by government agencies, so there is no requirement for clinical studies that support efficacy and exclude harm to fish - if a manufacturer finds a formulation that sells, they are all set. There are also less requirements to disclose the formulation and data about the effects of the product on different organisms, and surely there is less research done compared to how drugs for human use are studied.

Questions

Am I probably right about Chlorine Dioxide? If not, what is more likely?

Chlorine dioxide probably forms when chlorite reacts with organic matter, and not in the bottle.

If so would it be that it's chlorine + sodium chlorite that's actually in the bottle, and the chlorine dioxide gets created when added to the water?

There already is water in the bottle. Dry sodium chlorite is explosive. There is no evidence for the presence of chlorine in the bottle. The combination would be dangerous.

[OP in comments] ... increase aeration ...

In humans, sodium chlorite poisoning oxidizes hemoglobin to methemoglobin, lowering oxygen supply to the organs. High aeration might counteract slight toxicity to fish (at the recommended dosage).

Answer 2

The actual path I suspect is from the interaction of hypochlorous acid with ferrous ions in the tap water forming the powerful hydroxyl radical that can further interact with the aqueous $\ce{NaClO2}$. This could result in the liberation of $\ce{.ClO2}$ as claimed (being an alternate path to the standard lab prep cited, only arguably appropriate here with tap water and aeration).

Note: the following cited chemistry is advanced noting radical formations (including the stable $\ce{.ClO2}$ free radical).

First, the so-called Fenton-type reaction based on $\ce{HOCl}$ (in place of $\ce{H2O2}$ as in standard Fenton chemistry):

$\ce{Fe++ + HOCl -> Fe+++ + .OHCl-}$

At pH > 5 (or in presence of chloride):

$\ce{.OHCl- -> .OH + Cl-}$ k = 6.1 x 10^9 (Source: Supplementary Material and click on Supplement File 1 to download)

Next, the liberation of the stable free radical $\ce{.ClO2}$ radical with the help of the hydroxyl radical:

$\ce{.OH + ClO2- <-> OH- + .ClO2}$ (Source: "New insights into the decomposition mechanism of chlorine dioxide at alkaline pH")

where interestingly, this recent (2017) source cites this hydroxyl radical path as a possible avenue, to quote:

The generation of HO˙ could be one reason for cellulose degradation by ClO2 at alkaline pH, but possibly not the unique one, as it was not proved in this article, whether or not ClO2 is able to directly attach the OH functions of anhydrosugars at alkaline pH.

Further, to account for the statement: "It is suggested to always increase tank aeration during treatment to ensure there is an adequate oxygen supply for infected fish", this is likely the result of the following reaction involving so-called metal auto-oxidation forming the superoxide radical anion:

$\ce{Fe++ + O2 -> Fe+++ + .O2-}$ (Source: see, for example, this ACS article)

which is suspected further of interacting with $\ce{.ClO2}$ as follows:

$\ce{.ClO2 + .O2- -> ClO2- + O2}$ (Based on H2O2 as noted here)

reforming the chlorite, and thus even possibly cycling the disinfecting process, especially in the presence of sunlight and photosensitive Ferric chloride.

Supporting source: A Dutch study: Chlorine Dioxide as a Post-Disinfectant for Dutch Drinking Water, to quote:

In this paper, results are presented of experiments into the consumption and reaction kinetics of chlorine dioxide in a number of (drinking) waters in The Netherlands. It was found that chlorine dioxide consumption is related to the dissolved oxygen content (DOC) of the water and the reaction time.

I hope this, albeit, technical discussion helps with your understanding on what is likely occurring.

Answer 3

Spot on!

short answer, confirmation of your theory is all right here

Yes, Chlorine Dioxide ClO2 is being produced. Chlorite and Chlorine Dioxide are very similar. Chlorite is an ion and Chlorine Dioxide is that ion as a free radical (with an extra electron). As seen in the chart Karsten's answer gave, Chlorine Dioxide has an additional oxidative punch.

Both Chlorite and Chlorine Dioxide are well known and widely used throughout many industries. They are often preferred over other disinfectant compounds when health (such as food or water safety) is a concern. In your case, they are preferred over hypochlorite (bleach) or chlorine because they will not chlorinate like those compounds do, and only work via oxidation. As a bonus, molecular oxygen is left behind when ClO2 is fully reduced.

That's where you went a little off. No Chlorine gas is required to get Chlorine Dioxide from a chlorite solution. Putting Chlorine or a chlorinator like hypochlorite (HClO) into the bottle would defeat the gentle aim of the product: do no harm to fish. Correct me if I'm wrong, but didn't you already spend so much energy getting chlorine out of the tapwater when you filled the tank?

So, you noticed the oxidation of chlorite by chlorine to get chlorine dioxide but didn't find the more applicable method of simple acidification. Probably because you assumed the whole aquarium would have to lower in pH. No, everything is dynamic. You can have tiny pockets of acidity even in your alkaline tank. Pathogens often create acidity. They also join together and hide using biofilm. For both these reasons, chlorite is the right tool for the job.

Chlorite itself will oxidize, but not as strongly as the free radical Chlorine Dioxide.

What likely happens is the chlorite floats around until it encounters acute acidity at which point it can jump up an oxidation level to Chlorine Dioxide which will oxidize any pathogen around, bacteria, virus, or fungus. Pathogens generally require and make acidity. With enough ClO2 the product can even tackle protozoa and multi-cellular pathogens, even ones with glutathione defense. The ClO2 would have to deplete that defense first of course, but as Karsten indicated in his answer, that's not a problem. Chlorine Dioxide is particularly effective against biofilm.

here's a quote from wikipedia, "Chlorine dioxide is also superior to chlorine when operating above pH 7, in the presence of ammonia and amines, and for the control of biofilms in water..." Chlorine dioxide is considered a selective oxidant because it generally spares organic matter. This is why it is preferentially used in the water, food, and medical industries.

So what is the mechanism?

Eventually oxidation of amino acids, and likely cysteine in particular. In larger organisms ClO2 oxidizes GSH to GSSG and leaves it there, generally not oxidizing further. When ClO2 oxidizes, O2 (molecular oxygen) is left behind. O2 being key for most life, especially the kind considered non-pathogenic, like your fish, or the beneficial aerobic microbes in your tank.

Now you might think, "Well this sounds great, Chlorine Dioxide can kill anything!" and you'd be right. Well, technically. Which brings us to Karsten's otherwise excellent answer and its faint aroma of fear-monger or concern-troll.

Kill Everything!

Sodium Chlorite, the active ingredient (and the active ingredient of "MMS," which Karsten brought up), can indeed oxidize hemoglobin at high enough concentrations. Also, at those concentrations your fish would be long dead. In fact, if you and your fish drank Chlorite solution in increasing concentration/doses your fish would likely die long before your methemoglobin creation became life-threatening. What's the fish equivalent of 'Canary in a coal mine?' Why is that? Just like the canary, they're smaller than you. that's all.

But wait, this product is perfectly safe for the fish, isn't it? Yep.

let's talk concentration.

MaracynOxy contains 4-5% "chlorite solution" as per the SDS. for comparison: MMS (infamous "Master Mineral Solution" referenced above) is a 22.8% chlorite solution. (although in fairness it is dosed in drops, a drop being 0.025-0.05mL) Aquamira water purifier tablets are 5-7% chlorite. Closys mouthwash is 0.1% or (1000ppm) chlorite. and here is an SDS for simply chlorite salt

at 5% concentration you have 0.12mg chlorite in 2.4mL dose .43mL of MMS would be needed. that's 8-10 drops or 120mL of Closys mouthwash

Karsten is keen to remind us how dangerous chlorite and chlorine dioxide is while supplying examples which contradict this. Chlorine Dioxide is so dangerous that it is preferentially used to disinfect meat in the food industry. He cites a study as evidence chlorite is so bad which concludes chlorite is less toxic than commonly used compounds in personal care products. He cites a very special enzyme unique to some bacteria (all aerobic, I assume) to deconstruct chlorite into harmless Chloride and molecular Oxygen. The implication being humans don't have that special dismutase. Quick question, when GSH (glutathione) reduces ClO2 what is left behind? any wild guesses?

Karsten neglected to remind us not to drink anhydrous ammonia, Hydrogen Peroxide, hand sanatizer, or isopropyl alcohol.

In the study Karsten cites concerning oxidative stress they demonstrate how chlorite depletes glutathione. The study also concludes chlorite has a lower toxicity to mammalian cells than benzalkonium chloride. Yes, chlorite is considered a less toxic oxidant than peroxides, sodium hypochlorite, or BZK. By the way, you are all absorbing BZK when you use many common eyedrops, eardrops, nasal sprays, hand sanitizers, antiseptic spray, wet-wipes, throat lozenges, mouthwash, disinfectant cleaners, and even spermicidal cream. BZK is (relatively) safely used in all of these products applied on or in the body even though this study showed Chlorite to be less toxic.

BZK is genotoxic (it damages DNA), causes cellular damage, alteration in catalase activity, acetylcholinesterase activity, and lipid peroxidation 10.1016/j.etap.2016.04.016. But sure, BZK doesn't affect glutathione.

Chlorine dioxide is the preferred compound for treating cooking fats and oils.

Why? It does NOT cause lipid oxidation.

It is precisely the presence of glutathione and the mild way in which chlorite and chlorine dioxide oxide GSH which make it effective in killing smaller organisms while leaving bigger ones. A virus doesn't have glutathione. Chlorine dioxide will bust that cysteine or histidine on the virus structure and now the virus is in pieces. Similar things happen to fungus and bacteria and simple multi-celled organisms too. The bigger the organism, the more complex, and the more resources and tools it has to deal with oxidation. This is why the fungus dies but the fish don't. Now if you bought the 16 oz bottle and decided instead of reading the directions you would just dump the whole thing in you would probably get some floating fish.

that brings us to a medical case of MMS

(chlorite solution) ingestion requiring a hospital visit (cited in Karsten's answer). In the study they very scientifically tell us the child ingested 'a small amount.' Well, a 'small amount' of a substance dosed in drops isn't small at all. what are we talking, 10mL? 30mL? that's 2.8mg and 8.4mg of chlorite respectively and 66-200 times the usual adult starting dose of 3 drops. What substance that is generally safe at regular doses is ever taken at 66-200 times? Would that substance still be considered safe? A usual 'dose' of water is 8 oz, let's say 250mL. who here has taken 16.5L of water at one time? 50L? Anyone care to imagine what might happen if you did? If a child did so, would the parent take that child to the hospital? I would think so considering that's over 10% the LD50 for water. That child's life may very well be in danger. (LD50 of chlorite can be found in its SDS cited above. it's 284mg/kg in rats. rat to human dose conversion is generally 0.162x in mg/kg, so if the oral LD50 of chlorite for rats is 284mg/kg we get the HED (human equivalent dose) of 46mg/kg of chlorite which for a 60kg human would mean ingestion of 2.76g to achieve LD50. a 30kg 9-10yo child would be half that.)

The whole 16oz bottle of Maracyn Oxy would be 23.65mg of chlorite and if it didn't kill your fish, especially the smaller ones, it would very likely make them sick. By the way, the LC50 to minnows for Chlorine dioxide is 20ppm concentration over 96hrs.

With Chlorine Dioxide you see gentle vital use after gentle vital use, right up until mention of MMS and instantly the compound is transformed into the most caustic and destructive chemical known to man. Curious. And yet the very same outlets decrying Chlorine Dioxide as terribly toxic and dangerous are keen to promote NO, another free radical associated with wild health claims. Go figure!

Does Chlorine Dioxide have legitimate health claims?

I'm not making any here, but clearly many do make such claims, and it isn't all from kooks either. The compound is well researched but the health research is sparse, only beginning to pick up. It stands to reason organisms utilizing oxidative phosphorylation would benefit from readily accessible O2, hypoxia being a driver of disease. And that's in addition to any pathogen-killing (eg in blood) or biofilm dissolving (eg in bowels) action. As always, appropriate concentration and dose are vitally important.

Methylene Blue solves methemoglobin, if anyone is curious. Also happens to be another common active ingredient in aquarium treatment. And another unpatentable compound with seriously wild health claims (backed by research), which I wouldn't recommend you down entire bottles of or even mouthfuls.

and yes, UV would mess with the chlorite, UV is also redundant since the chlorite is doing the disinfection already.

boy this answer needs some more editing! meh.